Important Books & Reports

Glyphosate/Roundup, falsely claimed by Monsanto to be safe and harmless, has become the world’s most widely and pervasively used herbicide; it has brought rising tides of birth defects, cancers, fatal kidney disease, sterility, and dozens of other illnesses - more

Ban GMOs Now - Dr. Mae-Wan Ho and Dr. Eva Sirinathsinghji

Health & environmental hazards
especially in the light of the new genetics - more

Living Rainbow H2O - Dr. Mae-Wan Ho

A unique synthesis of the latest findings in the quantum physics and chemistry of water that tells you why water is the “means, medium, and message of life” - more

The Rainbow and the Worm - the Physics of Organisms - Dr. Mae-Wan Ho

“Probably the Most Important Book for the Coming Scientific Revolution” - more

I-SIS News no.3

Written and compiled by Mae-Wan Ho & Angela Ryan

Institute of Science in Society and Department of Biological Sciences, Open University, U.K.

From Seattle to Montreal - World Scientists Calling for GM Moratorium Swell to Over 230

Seattle was a truly inspiring event for the global civil society, every
sector was represented from all over the world: labour, family farmers,
indigenous peoples, professionals, consumer organisations, citizen action
groups, environmentalists. Suddenly, everyone realizes we are all struggling
against the same thing: corporate rule under a globalised economy that has
created massive poverty and brought the earth to the edge of extinction. And
still, our governments in the industrialized North are bent on negotiating
agreements behind closed doors at the WTO that will effectively sacrifice
environmental protection, labour and safety standards, and even basic human
rights to trade and financial imperatives. Fortunately for everyone,
governments from the Third World and other non-industrialized countries have
united to say a resounding No! on our behalf.

Our Open Letter from World Scientists to All Governments, calling for a
GM moratorium, a ban on biopatents and a public enquiry into the future of food
security (see ISIS website) was successfully delivered to the Heads of
Delegation to the WTO, thanks to the Third World Network. In the event, 144
scientists from 27 countries were included. Our letter was particularly timely
as Canada and Japan proposed to set up a Biotechnology Working Group in the WTO
to deal with GMOs and biotechnology, while the United States called for
improvements to rules and disciplines of the WTO to ensure that trade in
agricultural biotechnology products is based on "transparent, predictable and
timely processes".

The aim of the proposals, as pointed out by Mathew Stilwell of the
Center for International Environmental Law and Martin Khor of the Third World
Network, is to limit the ability of importing countries to regulate GM products
and to subordinate the International Biosafety Protocol, currently being
negotiated under the Convention on Biological Diversity, to the WTO. The
proposals were a blatant attempt to undermine the Biosafety Protocol and to
force trade of GMOs in the face of serious threats to health and biodiversity.
They were strongly opposed by the like-minded group which included the African
region, the Caribbean and most countries in the Third World.

In the event, an estimated 35 000 to 50 000 took part in peaceful
demonstrations in the city. Yes, it was overwhelmingly peaceful despite
aggressive tear-gassing, pepper sprays, rubber bullets and other tactics
employed by the Seattle police, and a few shop windows broken as a consequence.
Michael Meacher, UK Minister for the Environment, gave an accurate account in
his diary for the Independent on Sunday, and definitely blames the
Seattle police. The police chief has resigned amid calls for a public
enquiry.

The official WTO negotiations collapsed  to great jubilation in
the streets - after the government delegations of the developing nations united
in protesting against the lack of transparency and democracy in the
proceedings. The rich industrialized nations again tried to impose their
corporate agenda on the poor countries, and failed. It was a decisive victory
for the developing countries and for all citizens of civil society in their
collective struggles against corporate feudalism.

But, beware of the next round: the up-coming Biosafety Protocol meeting
in Montreal, starting 25 January 2000, when GMOs and products thereof will take
centre stage. We shall be submitting our letter to the official delegations
there. Since Seattle, the number of scientists who have signed on has jumped to
over 230, thanks to Jaan Surkuula, Director of Pysicians and Scientists for
Responsible Assessment of Science and Technology (PSRAST) and signatories to
their statement who have joined forces with us, plus others who have signed on
independently. Please help collect more signatures for Montreal! It will be a
very crucial meeting, and we must make sure that the arguments of real
scientists who adopt the ecological perspective and the precautionary approach
are heard loud and clear.

At least ten scientists on our list were active in Seattle, in the
teach-ins, workshops as well as the street demonstrations (none got arrested,
fortunately): Dr. Phil Bereano of Council for Responsible Genetics USA; Dr.
Tewolde Egziabher of Ministry of the Environment, Ethiopia and Spokesperson for
the African Region and Like-minded Group on Biosafety; Dr. Michael Fox of
Council for Responsible Genetics USA; Dr. Mae-Wan Ho of ISIS and Open
University UK; Dr. Jonathan King, Molecular Biologist, MIT, USA; Dr. Peter M.
Rosset of Institute for Food and Development Policy, USA; Devinder Sharma of
Forum for Biotechnology and Food Security India; Dr. Vandana Shiva, Research
Foundation for Science and Ecology India; Dr. David Suzuki of the Suzuki
Foundation and University of British Columbia Canada; and Dr. Christine von
Weisaeker, Ecoropa Germany. (M.W.H.)

Pusztai has published amidst a fresh storm of attack, and even reported
threats to the Editor of The Lancet (see Ewen, S. and Pusztai, A.
(1999). Effect of diets containing genetically modified potatoes expressing
Galanthus nivalis lectin on rat small intestine. The Lancet 354,
1353-4; also http://plab.ku.dk/tcbh/PusztaiPusztai.htm
for Pusztais full rebuttal to his critics). The controversy reveals the
sorry state of the so-called sound science which his critics
purports to defend, and highlights the general disregard for the precautionary
principle in current risk assessment.

GM potatoes expressing a snowdrop lectin (GNA) under the cauliflower
mosaic viral (CaMV) 35S promoter have been developed to increase insect and
nematode resistance. GNA was chosen because previous studies by the authors
showed the effects of the lectin on the rat small bowel have been
minimal, at least when fed on large amounts of the lectin for ten
days or less. Pusztais collaborator, Stanley Ewen, examined the
microscopic structure of the lining of different parts of the rat gut in groups
of animals fed for ten days, respectively, on non-GM potatoes, GM-potatoes and
non-GM potatoes spiked with the GNA protein. All the diets had the same protein
and energy content.

Variable effects were found in different parts of the gut. In the
stomach, a highly significant proliferation of the lining was found in both
rats fed GM potatoes and those fed non-GM potatoes spiked with lectin. It was
reasonable to conclude, therefore, that the effect on the stomach lining was
mainly due to the expression of the GNA transgene. However, significant changes
in the lining of the small intestine and parts of the large intestine were
found only in the group of rats fed GM potatoes. Ewen and Pusztai conclude that
"other parts of the construct or the genetic transformation (or both) could
also have contributed to the overall biological effects of the GNA-GM
potatoes." In addition, rats fed GM potatoes also had significantly increased
lymphocytes (white blood cells) in the gut lining, which indicates damage to
the intestine.

The explosive claim is that "other parts of the construct or the
genetic transformation process" may be toxic. If that were the case, all
GM crops may not be safe. Elsewhere, Pusztai has questioned the safety of the
cauliflower mosaic viral promoter in the transgenic potatoes which is in
practically all current GM crops. Could the signs of damage to the intestine be
due to viral infection? That was a claim made in Pusztais earlier
comunications, though not in the present publication. If so, might the
cauliflower mosaic viral promoter have anything to do with it? (see Viral Gene
Switch  A Recipe for Disaster? This issue)

Neither Pusztai nor Ewen regards their research as definitive proof that
GM potatoes, or GM food in general is harmful. Pusztai has repeatedly
stressed the need for further research. However, the results do throw into
serious doubt the claim of the biotech industry and regulatory authorities that
GM food is safe. According to a leading British statistician, one
should be worried about safety if even a single rat had been affected.

The attacks on Pusztai say more about the sorry state of the so-called
sound science that lies behind current risk assessment, whether it
be for radioactive discharge, industrial chemicals, toxic wastes or GMO. It is
a reductionist, mechanistic science that ignores the complexity and
interdependence of living systems, that has, furthermore, been thoroughly
discredited by recent scientific findings (see Genetic Engineering Dream or
Nightmare? Featured in Book Briefs, this issue). More importantly, it is
directly in conflict with the precautionary principle that has been accepted in
several international conventions including the Convention of Biological
Diversity and the EU (see an excellent recent publication, Protecting Public
Health & the Environment, featured in Book Briefs, this issue).

As applied to GMOs, the principle may be stated as follows: where there
is scientific evidence to suspect serious irreversible harm, lack of scientific
certainty or consensus should not be used as justification for taking
preventative measures. This is based on that offered in another important
recent publication, An Orphan in Science: Environment Risks of Genetic
Engineered Vaccines, (see Book Briefs, this issue), and in line with that
adopted by Swedish law for hazardous and chemical products.

Risk assessment based on what Pusztais critics refer to as
sound science not only ignores the complexity and interdependence
of real living systems and reasonable suspicion of harm based on scientific
evidence, it also places the onus on regulators and civil society to
demonstrate that something is definitely harmful before it can be refused
approval, withdrawn or banned. It is such systematic misuse and abuse of
scientific evidence that has continued to allow corporations to endanger human
health, destroy wild-life and our planet with impunity. No wonder there is a
debate on whether risk assessment should be science-based at all.

We believe that risk-assessment should be science-based, but it should
be based on real, reliable science whose goal is to enable us to live
sustainably with nature. In contrast to his critics, Pusztai has behaved with
integrity and social responsibility as a scientist, which is fully in
accordance with the precautionary principle. (M.W.H.)

Viral Gene Switch  A Recipe for Disaster?

This story highlights the hazardous nature of the genetic engineering
process as well as the new gene constructs created and released into the
environment.

A scientific paper on the cauliflower mosaic viral promoter (CaMV
promoter) has attracted at least nine attacks, including one from Monsanto,
before it is actually published. The attacks and rebuttals have been
ricocheting around the web, but what is it all about? (Please visit ISIS
website for the paper, Ho, M.W., Ryan, A. and Cummins, J. (1999). The
cauliflower mosaic viral promoter  a recipe for disaster? Microbial
Ecology in Health and Disease (in press), and the official authors
reply to critiques.)

Prof. Joe Cummins of the University of Western Ontario was the first
scientist to question the safety of the cauliflower mosaic viral (CaMV)
promoter, which is in practically all GM crops currently grown commercially or
undergoing field trials. He pointed out that the promoter could recombine with
other viruses to generate new disease-causing viruses. In our joint paper, we
review some recent findings which give further grounds for concern, and
recommend the immediate withdrawal of all crops and products containing the
CaMV promoter, which effectively means all commercial and field tested GM
crops, and products with incompletely degraded DNA.

The story begins with the promoter. A promoter
is a stretch of genetic material that acts as a switch for turning genes on.
Every gene needs a promoter in order to work, or to become expressed. But the
promoter is not a simple switch like that for an electric light, for example,
which has only two positions, either fully on or fully off. Instead, the gene
promoter has many different parts or modules that act as sensors, to enable it
to respond, in ways we do not yet fully understand, to signals from other genes
and from the environment. These signals tell it when and where to switch on, by
how much and for how long. And under certain circumstances, the promoter may be
silenced, so that it is off all the time.

The role of the promoter of a normal gene in an organism is to enable
the gene to work appropriately in the extremely complex regulatory circuits of
the organism as a whole. The promoter associated with each of the
organisms own genes is adapted to its gene, while the totality of all the
genes of the organism have been adapted to stay and work together for millions,
if not hundreds of millions of years. The genome of each organism is organized
in a particular way which is more or less constant across the species, so
individuals within a species can freely interbreed. Each species protects its
integrity and remains genetically stable because there are biological barriers
which prevent distant species from interbreeding or otherwise exchanging
genetic material. Foreign DNA is generally broken down or put out of action.
Genetic engineering attempts to overcome these biological barriers so genes can
be arbitrarily transferred between species that would never interbreed in
nature. In order to do so, special tricks are needed.

When genetic engineers transfer foreign genes into an organism to make a
GMO, they also have to put a promoter in front of each of the genes
transferred, otherwise it would not work. The promoter plus the gene it
switches on make up a gene-expression cassette. Many of the genes
are from bacteria and viruses, and the most commonly used promoter is from the
caulifower mosaic virus. Several gene-expression cassettes are usually stacked,
or linked in series, one or more of them will be genes that code for antibiotic
resistance, which will enable those cells that have taken up the foreign genes
to be selected with antibiotics. The stacked cassettes are then spliced in turn
into an artificial gene carrier or vector. The vector itself is
generally made by joining together parts of viruses and other infectious
genetic parasites (plasmids and transposons) that cause diseases or spread
antibiotic and drug resistance genes. In the case of plants, the most widely
used vector is the T-DNA which is part of the tumour-inducing
plasmid (Ti plasmid) of Agrobacterium, a soil bacterium that
infects plants and give rise to plant tumours or galls.

The role of the vector is to smuggle genes into cells that would
otherwise exclude them. And more importantly, the vector can jump into the
cells genome and so enable the gene-expression cassettes it carries to
become incorporated into the genetic material of the cell. The genetic engineer
cannot control where and in what form the vector jumps into the genetic
material of the cell, however. And this is where the first unpredictable
effects can arise. Each transgenic line or GMO is unique, and gives rise to
different unintended effects. In the case of food, this can mean unexpected
toxins and allergens (see GM Soya & Increased Soya Allergy in Science
Notes, this issue).

The foreign genetic material in the GMO  referred to as the
transgenic DNA or the construct  is quite
complicated. It consists of new genes and new combinations of genes - from
diverse species and their genetic parasites - that have never existed in
nature. Such chimaeric constructs are already known to be structurally
unstable, that is, they have a tendency to break and join up and rearrange. It
is to be expected that such structural instability can only increase when the
construct is introduced, by a hit or miss process, into a new genome. The
instability of GMOs is a big problem for the industry. GMOs often do not breed
true (Terminator in New Guises, this issue).

Why use a promoter from a virus such as the CaMV? Like all viruses, CaMV
is a genetic parasite that has the capability to infect cells and hi-jack the
cell to make many copies of itself in a short period of time. Its promoter is
therefore very aggressive, and is also found to be active in all plants,
monocots, dicots, algae, and the E. coli bacteria that live in the gut
of all mammals. Hence, the CaMV promoter is very popular with genetic
engineers. It effectively makes the gene placed next to it turn on full blast
in any plant genome, at perhaps a thousand times the volume of any of the
organisms own gene. Having it in the genome is rather like having the
loudest phrase of a heavy-metal piece, played with the most powerful amplifier,
over and over again, throughout a live performance of a Mozart concerto. What
the CaMVpromoter does is to place the foreign gene outside the normal
regulatory circuits of the host organism, subjecting the host organism to
unremitting metabolic stress. This will multiply the unintended, unpredictable
effects in the GMO. It may also be another reason why GMOs are notoriously
unstable (Finnegan, J. & McElroy, D. 1994, Bio/Technology 12, 883). The
organism generally reacts to the presence of foreign genetic material by
breaking it down or putting it out of action in other ways. Even after the
genetic material is incorporated into the genome, it can silence the foreign
genes so they are no longer expressed (see Terminator in New Guises, this
issue).

The key recent finding, which provoked us to write our paper, was the
report by Kohli et al, (1999) The Plant Journal 17, 591, that the
CaMV promoter contains a recombination hotspot  a site where
the DNA tends to break and join up with other DNA, thus changing the
combination and arrangement of genes. Around the hotspot are several short
stretches, or modules, for binding various enzymes, all of which are also
involved in recombination , ie, breaking and joining DNA. Furthermore, the CaMV
promoter recombination hotspot strongly resembles the borders of the T-DNA
vector carrying the transgenes, which are also known to be prone to
recombination. It is that which enables the vector to invade the cells
genome in the first place.

The aim of our original paper, restated explicitly in our official
rebuttal, was to review the relevant findings and, in particular, to point out
the implications which the researchers themselves are unwilling or
unable to draw. The findings that transgenic DNA has the tendency to break and
join in several places imply that parts or all of it may be more likely than
the plants own DNA to jump out of the genome and successfully transfer
horizontally to unrelated species. Horizontal gene transfer, in this context,
means the transfer of the genetic material directly by infection to the genetic
material of unrelated species, in principle to all species interacting with the
GMO: bacteria, fungi, earthworms, nematodes, protozoa, insects, small mammals
and human beings. This process is uncontrollable and cannot be recalled.
Transgenic DNA has been designed to be invasive and to overcome species
barriers; once released, it will invade different organisms especially bacteria
which are in all environments, where it will multiply, mutate and recombine.

There are additional findings which suggest an increased potential for
transgenic DNA to spread horizontally. For example, the enzymes in the cell
that insert the transgenic DNA into the genome can also make it jump out again.
DNA released from both dead or live cells can survive without being degraded in
all environments, including the mouth and gut of mammals. DNA can be readily
taken up into cells. And all cells can take up naked or free DNA. A
recent finding suggests that integrated viral sequences are preferentially
taken up and incorporated into the cells genome (see Reusable DNA Alert,
this issue). The instability of transgenic DNA may also be enhanced as the
result of the metabolic stress inflicted on the organism by the CaMVpromoter
which gives rise to continuous over-expression of transgenes.

The major consequences of the horizontal transfer of transgenic DNA are
the spread of antibiotic resistance marker genes among bacteria and the
generation of new bacteria and new viruses that cause diseases from the many
bacterial and viral genes used. The generation of new viruses could occur by
recombination with live or dormant viruses which we now know to be present in
all genomes, plants and animals included. Recombination with defective, dormant
animal viral promoters may also occur, as we know that there are modules which
are interchangeable between plant and animal promoters. Recombination of CaMV
promoter modules with defective promoters of animal viruses may result in
recombinant promoters that are active in animal cells. This
may reactivate the virus, generate new viruses or give
functional viral promoters causing
over-expression of one or another of dozens of cellular genes which are now
believed to be associated with cancer.

In conclusion, there is sufficient scientific evidence to support
well-founded suspicion of serious, irreversible harm to justify the immediate
withdrawal of all GM crops and products containing the CaMV promoter from
environmental release. This is fully in accord with the precautionary
principle. (M.W.H.)

Terminator Technology In New Guises

The terminator technology, which genetic engineers harvested seeds not
to germinate, was vigorously opposed by farmers and consumers all over the
world. One of the claimed benefits is that it prevents the spread of
transgenes, but its real purpose is to protect corporate patents on seed. It
offers no benefit to farmers or consumers. In response to widespread
opposition, Monsanto has recently announced that it will not commercialize
terminator seeds, if only because such seeds are not yet available. But
research is continuing.

In fact, terminator technology has continued to be developed under a
number of different guises. The main one is Genetic Use Restriction
Technologies (GURT) ( see Traitor Tech. The Terminator's Wider
Implications. RAFI Communique, Janurary/February, 1999). Newer versions
make seeds dependent on the application of a chemical for germination, or for
expressing the desired transgenic trait  the chemical being exclusively
manufactured by the company selling the seeds, so the end result is again to
protect corporate patents.

Genetic engineering is not a precise technology. On the contrary, it is
uncontrollable, unreliable and unpredictable (see Viral Gene Switch  A
Recipe for Disaster?). The GURT technologies are worse. They depend on
site-specific recombination  breaking and joining DNA at two
specific sites recognised by a recombinase enzyme, which then snips out the DNA
between the two sites. The two sites might flank a blocking sequence within a
promoter, so removal of the blocking sequence will enable a gene to be
expressed which makes a poison to prevent the seed from germinating, for
example. Or it may do the opposite, the sites may flank the promoter itself
which is necessary for expressing the gene, so when it is removed, the gene
will no longer be expressed, and the seed will germinate. The gene coding for
the recombinase enzyme is engineered to be under the control of the external
stimulus, ie, the chemical manufactured exclusively by the company, so the
recombinase will be active only when the chemical is applied.

Thus, GURT technologies involve multiple feats of precise gene stacking,
inserting the gene stacks into plants in exactly the configurations
constructed, and subsequent to that, precise regulation in the transgenic
plant(s), and exactly predictable response of the recombinase to the external
chemical stimulus. However, those requirements for precision are beyond the
capability of the genetic engineer. The hazards of the transgenic DNA resulting
from GURT technologies are much greater, because the imprecisions of inserting
multiple gene-constructs are multiplied, and also because of the site-specific
recombination mechanisms deliberately introduced. Recombination creates new
combinations of genes and has the potential to scramble genes and genomes when
it is imprecise. It is already known that recognition between designated
recombination sites and their enzymes (recombinases) are far from exact (see
Kohli et al, 1999, The Plant Journal 17, 591) and many mistakes are
anticipated. These genes  the recombinase and the recombination sites -
once engineered into the plants, will spread both by ordinary cross-pollination
and by horizontal gene transfer, multiplying the opportunities for scrambling
or rearranging genes and genomes.

Now, a new report claims to have used site-specific recombination to
solve one problem of imprecision in genetic engineering plants, which is that
multiple copies of the foreign genes tend to be inserted at each site
(Srivastava, V., Anderson, O.D. and Ow, D.W. (1999). Single-copy transgenic
wheat generated through the resolution of complex integration patterns.
Proc. Nat. Acad. Sci, USA 96, 11117-21). As pointed out by the authors,
multiple copies are undesirable because it often leads to transgene
instability, either on account of gene-silencing by the host organism, or
structural instability such as recombination between multiple copies which
result in the loss of the transgene.

To solve the problem, the researchers constructed vectors consisting of
transgenes flanked by recombination sites that are inverted (so they are
not recognized by the recombinase). When the transgene is integrated into the
wheat genome in a repeated configuration, the recombinase will only snip out
the block of genes between sites that are in the same orientation, so
ultimately, only one single copy of the transgene will be left at each site, at
least in theory. However, it is clear that many unexpected results were also
obtained alongside the expected, including the inversion of genes (literally
genes turned around), scrambled transgene configuration and scrambled host
genome, often arising from the imprecise action of the site-specific
recombinase. The authors admit the possibility of scrambling and removing host
genome DNA in their procedure, and recommends obtaining single-copy transgenic
lines from several different progenitor lines.

In our view, genes and constructs involving site-specific recombination
systems should not be approved for release into the environment in any form.
(M.W.H.)

Biopatents

Biopiracy Exposed

Eleven indigenous peoples organisations, collectively known as the
Council of Indigenous Traditional Midwives and Healers of Chiapas, are
demanding that a US Govt. funded bioprospecting programme suspend its
activities in Chiapas, Mexico, and are asking other indigenous people in
Chiapas to refuse to cooperate with the researchers (RAFI 1/12/99 news
release). But U. Georgia (US), cooperatiing with a Mexican university research
centre, El Colegia de la Frontera Sur (ECOSUR), and Molecular Nature Ltd., a
biotech company based in Wales, UK, refuse to halt the five-year project which
aims to collect and evaluate thousands of plants and microorganisms used in
traditional medicine by Mayan communities.

Sebastian Luna, an indigenous Tzeltal spokesperson, refers to the
project as a robbery of traditional indigenous knowledge and resources. It
explicitly proposes to patent and privatize resources and knowledge that have
always been collectively owned. It create conflicts within the communities as
some individuals are collaborating with the researchers for a few pesos or
tools.

Dr. Alejandro Nadal, researcher at Colegio de Mexico has denounced
another biodiversity contract in Mexico signed by the Universidad Autonoma de
Mexico (UNAM) between Diversa Corporation (US) in which researchers are obliged
to provide samples of unique micro-organisms from natural protected areas of
Mexico to Diversa for a mere &S$50 per sample.

Our governments and academic institutions should stop these immoral,
unlawful acts of biopiracy and respect indigenous communities rights over
their collective knowledge and biological resources. (M.W.H.)

Biopiracy Patents Revoked

An important victory was won by indigenous peoples from nine South
American countries as US Patent and Trademark Office announced the cancellation
of a US patent for the the "ayahuasca" vine, Banisteriopsis caapi, which is
native to the Amazonian rainforest (Center for International Environmental Law
(CIEL) press release, 4.11.99). Thousands of indigenous peoples in the region
use the vine in traditional religious and healing ceremonies. PTOs
decision came in response to a request for re-examination of the patent filed
in March by Coordinating Body for the Indigenous Organization of the Amazon
Basin (COICA), the coalition of Amazonian Peoples and Their Environment, and
lawyers at CIEL.

The PTO based its rejection of the patent on the fact that publications
describing Banisteriopsis caapi were "known and available" prior to the
filing of the patent application. This will set the precedent for revoking
other similar patents which have been awarded. In a separate proceeding at the
PTO, the three groups have called for changes in the PTO rules that allow
patent claims based on traditional knowledge and use by indigenous peoples.
Applicants should identify all biological resources and traditional knowledge
that they used in developing the claimed invention, and should disclose the
geographical origin, and provide evidence that the source country and
indigenous community consented to its use. (M.W.H.)

EU Biopatents Directive Opposed

German Minister of Justice Herta Daeubler-Gmelin stated in letter to
Greenpeace that the European Patents Offices decision last June to
implement the EU Directive on patenting was illegal, according to a Greenpeace
Germany press release (1.12.99). Since Sept. 1, the EPO is allowing patents on
plants and animals, as well as patents on human genes and parts of the human
body. The German Ministry at first approved the decision in June, only to
withdraw in October. The latest German decision was in accord with that taken
by France, who had voted against the implementing regulations in June.

The unexpected decision by the EPO last June was the initiative of the
President of the Office, Ingo Kober, who in doing so, fulfilled the wishes of
the genetic engineering industry. The implementation will enable private
corporations to sequence and patent the human genome. Scientist who have
recently sequenced the human chromosome 22, had to publish their results
promptly in order to prevent a commercial company from patenting the whole
chromosome patented. But particular genes on chromosome 22 may already have
been patented. (M.W.H. & A.R.)

Gene Patents Stall Cures and Research

Medical research aimed at developing screening methods and cures for
congenital diseases are being stifled by corporate patents on human genes,
according to a front page report in the Guardian (15.12.99). A survey of US
laboratories found that a quarter of American research laboratories have
received letters from lawyers acting on behalf of biotech companies demanding
that they stop carrying out clinical tests for Alzheimers disease breast
cancer and other disorders, because their patents are infringed. Companies
holding patents are demanding high fees for testing, or for licensing the
tests. Half of the laboratories surveyed have stopped work on developing
screening because they know a patent had been licensed or is pending.

A group of American doctors and scientists have issued a protest that
these patents and exorbitant licensing fees are limiting "access to medical
care, jeopardizing the quality of medical care and unreasonably raising its
cost".

Jonathan King, genetic researcher at MIT (and signatory to our World
Scientists Statement), points out that research is being stifled also because
of the culture of secrecy that now surrounds scientific research; "Its a
common experience at scientific meetings for people to withhold information
because they have a patent pending. Progress is being slowed down."
(M.W.H.)

Science Notes

Reusable DNA Alert

The genetic material of dead cells is scavenged by other cells. It is
taken up by phagocytosis  a kind of eating response in which the
cell envelops the material  and is then either metabolised to generate
energy and raw materials for building the cell, or it may be incorporated into
the genome of the cell. Integrated viral sequences may be preferentially
incorporated.

Researchers used DNA from killed human lymphoid cell lines with
integrated Epstein-Barr virus (EBV) as marker to follow the fate and expression
pattern of the DNA taken up by various other cell lines. The lymphoid cells
were killed by an irradiation procedure or a drug that fragmented DNA, and then
added to cultures of human fibroblasts, macrophages, or bovine aortic
endothelial cells. They found that all the living cells took up the DNA from
the killed lymphoid cells, but only DNA from lymphoid cell lines with
integrated EBV resulted in expression of viral genes and incorporation of DNA
containing viral sequences into the cells genome. DNA from killed
lymphoid cell-lines with non-integrated EBV (existing as episomes) did not
result in expression of viral genes, suggesting that viral sequences were not
incorporated into the living cells genome.

The researchers also found that the frequency of horizontal transfer of
human DNA to the genome of bovine cells was greatly increased in DNA from
lymphoid lines with integrated EBV compared with the same lymphoid lines
without any integrated EBV; furthermore, almost all of the transferred DNA was
associated with the integrated EBV. It suggests that the integrated EBV may be
preferentially transferred and incorporated. The authors conclude, "we
speculate that similar mechanisms of horizontal DNA transfer may be of
importance in conditions characterized by high levels of apoptosis [ie, cell
death], eg, in tumours treated with irradiation or chemotherapy".

Our comment: The results suggest that integrated viral sequences may be
more invasive than other parts of the genetic material. This is in line with
our suggestion that transgenic DNA may be more prone to transfer horizontally
(see Viral Gene Switch  A Recipe for Disaster? This issue). Also, the
authors speculation that similar mechanisms of horizontal DNA transfer
may occur in tumours treated with irradiation or chemotherapy raises questions
on the possibility that such treatments may spread cancer to other cells,
assuming that the EBV is an important causal agent of tumour-formation.
(M.W.H.)

GM Soya and Increased Soya-associated
Allergy

Scientists at the York Nutritional Laboratory have announced that soya
food allergy among the British public have unexpectedly risen 50% between 1998
and 1999. Soya is now in 9th position on the list of top serum reactive (test
for allergenicity) foods, up from 14th place in 1997. This finding
coincides with the large increase in imported foods from the US containing GM
soya.

Monsanto's GM soya, approved in 1996, was found to contain a 26.7%
increase in a major allergen, trypsin-inhibitor, which is also a growth
inhibitor. Consistent with this result, the growth rate of male rats was found
to be inhibited by the GM soya. Monsanto has not tested all possible allergens.
These results warrant a complete withdrawal of GM soya, at least until evidence
that it is safe is obtained.

Troubled GM Soya Not Substantially Equivalent

Once again, Monsanto's Roundup Ready GM soya is shown up to be not
substantially equivalent to non GM counterparts. Bill Vencill
of the University of Georgia in Athens examined the effects of heat on GM soya
in laboratory growth chambers. In soil temperatures of 25 C or less
during the day, both GM and non GM varieties grew the same. But in warmer
soils, the GM beans had stunted growth and in soils reaching 45 C the
differences were marked - lower heights, yields and weights, and the stems
cracked and split open in every GM soya bean plant. This phenomenon
exposes the plant to secondary fungal infections and explains what may have
happened to crops during the two hottest growing seasons in southern states,
when there were substantial crop losses by farmers growing GM soya.

These results indicate changes in plant physiology caused by the
insertion of transgenes, which make the plant resistant to glyphosate -
Monsanto's Roundup. It has been shown that GM plants carrying these
genetic alterations produce 20 per cent more lignin, which is the tough, woody
form of cellulose. The bacterial enzyme that imparts resistance to
glyphosate affects a major metabolic pathway in the plant, which sends lignin
production 'into overdrive' says Vencill. This unexpected
side effect may have been what caused the GM plants to be more
brittle. Resistance to gluphosinate, by contrast, uses a gene that
enables plants to break down the herbicide, and such GM plants were not
effected by heat in this way. Monsanto declined to comment but said that
farmers could avoid the problem by choosing a variety of GM soya that is better
suited to hot conditions. Reference: NewScientist, News, November
20, 1999, "Splitting Headache" by Andy Coghlan.

Our comment: These physiological problems with Monsanto's Roundup
Ready GM soya beans clearly demonstrate the inadequacy of the principle of
substantial equivalence. In our 2nd update of concerns on the WSS, we
report Marc Lappe's findings that Monsanto's GM soya is non substantially
equivalent in having a reduced phytoestrogen content compared to its non GM
counterparts. The insertion of transgenes into a plant cell causes major
unpredictable, unintended, which cannot be detected by current tests purporting
to establish substantial equivalence and hence gain regulatory
approval as being safe for human consumption. (A.R. & M.W.H.)

Promiscuous Transposons in Over-drive Alert

A new marker system has been designed to follow gene transfer in
arthropods and many other phyla. It is thought to enable better control
strategies against agricultural pests and disease vectors. It relies on a
transposon-based transformation technique, which has been used extensively to
study insects. One of the major obstacles in the use of transposons has
been the difficulty in obtaining marker genes that will allow easy and reliable
identification of transgenic animals. The green fluorescent protein (GFP)
from the jellyfish Aequorea victoria is a universal marker and has been
shown to be active in both plant and animal kingdoms. A strong artificial
promoter has now been found that is hyperactive, regionally restricted and
universal. It contains three binding sites for Pax-6 homodimers in front
of a TATA box (3xP3), and has been shown to drive expression of an enhanced GFP
variant in the eye of fruitfly and in flour beetle. The evolutionary
conservation of Pax-6 in the eye development of insects and vertebrates means
that the 3xP3 promoter may be active in any photoreceptor cell. It has
been described as a master regulator in terms of function, and when
mediated by transposons, provides a powerful new technique for generating
transgenic organisms and studying a large group of pest species. The
construct is artificial in origin, universal in function and does not require
any other host-specific factors. It may therefore essentially function in
all animals that have eyes. It has been suggested that, should it be
coupled with a set of promiscuous transposon vectors, such a system could be
used to study almost any species. It is thought the system can be applied
to competitive wild-type strains, making it suitable for pest-management
programmes. Reference: Genetic Techniques: A universal marker for
transgenic insects. Nature 402, 370-371 (1999).

Our comment: This system is a useful research tool that should be
scrupulously contained within the laboratory. On no account should it be
released into the wild. The artificial promoter may be expressed in all
organisms that have eyes. Such a powerful universal promoter coupled with
promiscuous transposon vectors will transfer horizontally with disastrous
consequences. (A.R.)

New Ways to Silence Transgenes

Researchers at the John Innes Center in Norwich finds a new species of
small antisense RNA molecule involved in post transciptional gene silencing
(PTGS) in plants. PTGS represents a natural antiviral defense mechanism,
which works against any invasive foreign genetic element that finds expression.
Transgenic RNA in GM plants are frequently targeted by PTGS mechanisms
and this strongly suggests that transgenes are perceived as viruses by their
host cell. This study has detected antisense RNA that is uniform in
length - approx. 25 nt (nucleotides) and complementary to the targeted mRNA.
It has been term spoiler RNA for it forms a duplex with the
target RNA and promotes degradation as well as interfering with translation.
It has been shown to accumulate in cells, either when transgene
transcription or RNA virus replication is taking place. The size of
the spoiler RNA is also significant - it is small enough to move through the
plasmodesmata (pores between cells) and has been shown to spread into nearby
cells and activate PTGS elsewhere in the plant. The precise role of the
25nt RNAs in PTGS is yet to be elucidated, but it is suggested these are
components of a systemic signal and specificity determinant in PTGS.
Reference: Hamilton A.J, Baulcombe D.C (1999). Science 286,
950-952 also see "Silent Saboteurs" NewScientist, 6.11.99 p 25.

Our comments: This new discovery shows that GM plants respond to
transgenes in the same way they do viruses. Transgenic RNA transcripts
are produced at a very high copy number in GM plants and are under the control
of powerful promoters like the CaMV 35S promoter. Viral infection
causes metabolic stress in cells and can lead to PTGS. The same can now
be said of transgenic constructs in GM plants. Furthermore, the size and
migratory nature of the RNAs reveal how small neucleotides have very important
biological functions in cells. This calls for regulation of all naked or
free nucleic acids used in genetic engineering biotechnology, a point made
forefully by Traavik (1999). Too Early May be Too Late: Ecological Risks of
Naked DNA, Report to Directorate of Nature Management, Trondheim, Norway.
(A.R.)

Sleeping Viruses Lurk in Plant Genomes

A new study provides evidence of repeated integration of
pararetroviral-like sequences into the genome of tobacco at a copy number of
approx 10 000. Therefore, plant pararetroviruses may integrate much more
commonly into host chromosomes than has been previously thought.
Furthermore, the insertions are thought to have occurred by illegitimate
recombination. Plant viral sequences were thought to integrate rarely, if
at all, into host genomes and this new evidence calls for a reconsideration of
this view. This has considerable implications for plant
genome evolution as integrated pararetorviral DNA could act as an insertional
mutagen or contribute strong constitutive promoters to neighboring plant genes
or could accumulate to generate a new repetitive sequence family.
Reference; Jakowitsch J et al (1999) Integrated pararetroviral sequences
define a unique class of dispersed repetitive DNA in plants. PNAS Vol 96
No23 pp 13241-13246

Our comment: This paper provides evidence that dormant viral DNA
may be much more widespread in plant genomes than previously thought. It
highlights the need for more extensive research in this area and it also has a
bearing on the ecological impact of GM plants - although the authors of this
paper fail to mention this. The CaMV 35S promoter is a
pararetroviral-derived sequence used in most transgenic constructs, where it is
integrated at random into the host genome. Furthermore, it contains an
independent recombination hotspot and may therefore recombine with dormant
viral sequences, which are in some instances integrated at extraordinarily high
copy numbers and are also highly recombinogenic - as shown by the amount of
illegitimate recombination events detected in this study. This may result
in the reactivation of dormant viral sequences, novel epigenetic effects and
other genetic disruptions, all of which are potentially hazardous and
unpredictable (see Viral Gene Switch  A Recipe for Disaster? This issue).
(A.R.)

More on Bt-Toxin

A new study shows that Bt toxin is exudated from Bt-corn and remains
active in the soil, where it binds rapidly and tightly to clays and humic
acids. It also retains insecticidal properties and is protected against
microbial degradation by being bound to soil particles. This research
shows that the Bt toxin persists in various soils for at least 234 days (the
longest time studied). Unlike the bacterium, which produces the toxin in
a precursor form, Bt corn contains an inserted truncated cry1Ab gene that
encodes the active toxin. Larva of the tobacco hornworm were used to
verify that the toxin was active and when placed on a medium containing
exudates from Bt corn, stopped feeding and began to die after 2 to 3 days, and
had a mortality of 90 to 95 percent after 5 days.

The authors point out that 15 million acres of Bt corn were planted in
the US in 1998. Bt toxin that is released into soil from roots
would add to the amount of toxin introduced into soil from pollen and as a
result of incorporating plant residues into the soil after harvesting the crop.
Bt toxin in the rhizosphere will kill target pest but may also promote
the emergence of toxin-resistant target insects. Moreover,
receptors for the toxin can be found on beneficial non-target insects
which will also be killed, and this will have an impact on other organisms in
higher trophic levels, in other words, a major impact on biodiversity.
Reference: Deepak Saxena, Saul Flores, G, Stotzky (1999) Nature 402, 480,
p 480.

Our comment: The ecological impacts of GM plants producing bt
toxins are now clearly predictable, based on existing scientific evidence. The
immediate withdrawal of all bt-crops is the only responsibble course of action.
(A.R.)

Book Briefs

Against the Grain. Biotechnology and the Corporate Takeover of Your Food

by Marc Lappe and Britt Bailey, Common Courage Press, Monroe,
Maine, 1998. This is the book that Monsanto tried to suppress. It is
extremely well researched and reveals a great deal of vital information.
It is clear and carefully constructed, appealing to both scientist and
non scientist alike. It tackles every level of the GM debate: from the
farm to the plate; onto the laboratory bench and into the scientific
literature; from the global market place to the corruption of our food chain;
and reveals the real issues at the heart of world hunger. It presents
strong evidence, which is carried through with logical argument and reasoning.
It captures the far reaching ramifications, and demonstrates that the GM
debate is probably the most important debate of our time. It should be
compulsory reading for all undergraduates of the life sciences.
(A.R.)

An Orphan in Science: Environmental Risks of Genetically Engineered Vaccines,

This Report follows close at the heels of an earlier one by the same
author, Too Early May Be Too Late, The Ecological Risks of Naked DNA,
also written for the Directorate of Nature Management of the Norwegian
Government, both of which count as the most significant contributions to risk
assessment of genetic engineering biotechnology.

Genetically engineered vaccines are a major route for environmental
release of GMOs, and yet ecological risk assessment has never been
contemplated. The vaccines are used not only for human beings, but also in
veterinary medicine and fish farming. Traavik identifies the possible risks and
hazards, which, in his view and in accordance with the precautionary principle,
should demand preventative measures. In practice, however, the risks are
"considered non-existent from the medical and scientific points of view" simply
because no investigations addressing them have ever been done. It also betrays
the deplorable lack of ecological thinking in mainstream science and medicine,
as well as a disregard for the precautionary principle.

Traavik begins by describing the history of vaccination, the immune
response and the different kinds of vaccines used traditionally and their
relative efficacy. Then he goes on to examine the entire range of genetic
engineered vaccines currently being developed, which include naked recombinant
DNA and RNA containing viral sequences. He reviews the literature on the trials
of vaccines in animal models, then identifies the possible hazards involved.
Particularly revealing are a couple of more detailed case studies, as for
example, on the anti-rabies vaccine made with the vaccinia virus, which had
been widely used in anti-small pox immunizations earlier this century.

His conclusion is that, "from an ecological and environmental point of
view many first generation live, genetically engineered vaccines are inherently
unpredictable, possibly dangerous" and should not be used on a large scale
until the problems identified have been addressed and clarified. Some of the
main problems are as follows: the generation of new viruses by horizontal gene
transfer and recombination, the unpredictable changes in host range of
genetically engineered viruses and viral genomes, the infectious nature and
long persistence of naked nucleic acids used as vaccines.

Changes to the genetic material of viruses are known to alter their
infectivity and host range in unpredictable ways, so that previously
non-susceptible species become susceptible. Recombinant viruses have already
been isolated from wild-life and human beings as the result of the mass
immunization programmes with the vaccinia virus against small-pox. The
genetically engineered anti-rabies vaccine made from the vaccinia virus was
released in the early 1990s in food baits intended for wild foxes, against the
advice of a substantial number of scientists. These baits have obviously been
taken up by many, if not all, species of wild mammals. All of these will be
reservoirs for recombination and generation of new viruses. Naked DNA and RNA
are now known to be protected from degradation in all environments and to be
readily taken up by all cells (see Viral Gene Switch  A Recipe for
Disaster? This issue), and according to a very recent report, viral sequences
appear to be preferentially incorporated into the cells genome (see
Reusable DNA Alert, Science Notes). Cells taking up naked DNA include germ
cells, so people receiving vaccinations may be receiving germ-line genetic
modification at the same time. The safest vaccines, according to Terje, are
those consisting of purified viral proteins only; and he believes their
efficacy can be improved.

Terje fully acknowledges that the imperative to save lives is very
strong, especially in the short-term. However, the long term negative
ecological and health impacts may far outweigh short-term gains. One could add
that other measures have proven far more effective for preventing and
ameliorating infectious diseases. These measures are improvements in nutrition,
hygiene, and living conditions, clean drinking water, unpolluted environment,
and the eradication of poverty.

This is an authoritative account by a world-class virologist and cancer
researcher who is also sensitive to the need for alleviating human suffering
and protecting the environment. He sets a fine example for us all. I especially
urge all our regulators on biosafety to read this book and take its message to
heart. (M.W.H.)

Protecting Public Health & the Environment, Implementing the Precautionary Principle,

If you want to know why our governments are failing to regulate toxic
discharges, food additives, and GMOs to protect health and the environment, it
is because they are not acting in accordance with the precautionary principle.
Adopting such a principle will change our whole approach to environmental
policies and to regulation. This book tells you the reasons why and more
importantly, how the precautionary principle has been and can be implemented in
practice. In general terms, this principle calls for protective, preventative
actions of harm even when scientific evidence is uncertain. More importantly,
it shifts the burden of proof of safety to the perpetrators, instead of
demanding regulators and civil society to provide scientific proof of
harm. The WTO is operating against the precautionary principle when it
judged the EU ban on US growth-hormone injected beef illegal. This is how the
WTO undermines every single effort by citizens and governments all over the
world to protect health and the environment (For a list of examples, read
another important publication, Invisible Government,The World Trade
Organization: Global Government for the New Millenium? by Debi Barker &
Jerry Mander, International Forum on Globalization, San Francisco, 1999)

The present book is the collective effort of an impressive international
panel of public health professionals, lawyers, academics, environmentalists and
policy makers. It is replete with useful information and good examples. I
learned how Sweden has the best environmental law in Europe based on the
strongest version of the precautionary principle. In contrast, the UK, with a
long tradition of "scientific corporatism and elitism", prefers to adopt the
"long pipes and tall chimneys" approach to make optimal use of the waste
assimilative capacity of the environment. Even when pressed to adopt the
precautionary principle, its role is limited as is clear from the statement
given by the UK Government, which is worth quoting in full (see p. 30),

"Where there are significant risks of damage to the environment, [we]
will be prepared to take precautionary action to limit the use of potentially
dangerous materials or the spread of potentially dangerous pollutants, even
where scientific knowledge is not conclusive, if the balance of likely costs
and benefits justifies it. The precautionary principle applies particularly
where there are good grounds for judging either that action taken
promptly at comparatively low cost may avoid more costly damage later,
or that irreversible effects may follow if action is delayed (emphasis
added)"

This is scientific corporatism, an admission that scientific
evidence must bow to the profit motive. Everyone, but everyone should read this
book and agitate for the adoption of the strongest form of the precautionary
principle at all cost. Our life and the life of our planet depend on it.
(M.W.H.)

Genetic Engineering Dream or Nightmare? Turning the
Tide on The Brave New World of Bad Science and Big Business,

by Mae-Wan Ho, New Leaf and Gateway Books, Dublin, 1999.

This is an updated and revised edition of a book of almost the same
title (missing the phrase,"Turning the Tide on") published in 1998, which was
widely reviewed and sold out. Please see ISIS website. It is one of the very
few books that offers a complete perspective and critique on all areas of
genetic engineering biotechnology, the social and political implications, and
especially the discredited scientific paradigm driving and promoting the
technology. It is written for the whole range of general readers from ordinary
citizens to policy-makers. The science behind the technology is made
sufficiently accessible so readers can make up their own minds, in particular,
with regard to the dangers posed. The new edition has a lot of additional
scientific information and is improved for easier reading. more info (M.W.H.)

Imagine a World without the Monarch Butterflies. Awakening to the Hazards of Genetically Altered Foods,

by Alex Jack, One Peaceful World Press, Becket, Mass,
2000 This little book is like a mini encyclopedia on the GM debate over the
past few years. It contains all the important arguments and references
and even manages to put over a 'who's who' within the circles of active
resistance against GM foods and those on the opposing side. It is
undoubted at the cutting edge of the debate and is an essential reference book,
useful for anyone wanting to grasp hold of the issues quickly. (A.R.)